Population-specific frequencies for LRRK2 susceptibility variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium

Abstract

Background: Variants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease.

Methods: The Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries.

Results: Herein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups.

Conclusions: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.

Keywords: LRRK2; Parkinson's disease; association study; genetics.

Figure 1

Population-specific allele frequencies. A) Minor allele (C) frequency of p.M1646T in patients with PD and controls according to country. Larger boxes indicate larger sample sizes. Countries are ordered according to minor allele frequency (lowest to highest) in controls. Minor allele frequencies are connected by dashed lines within patients with PD and controls in order to enhance visual display. B) Minor allele (T) frequency of p.A419V in patients with PD and controls according to country in the Asian series. Larger boxes indicate larger sample sizes. Countries are ordered according to minor allele frequency (lowest to highest) in controls. Minor allele frequencies are connected by dashed lines within patients with PD and controls in order to enhance visual display. C) Frequency of the protective p.N551K-R1398H-K1423K (G-A-A) haplotype in patients with PD and controls according to country. Larger boxes indicate larger sample sizes. Countries are ordered according to haplotype frequency (lowest to highest) in controls. Haplotype frequencies are connected by dashed lines within patients with PD and controls in order to enhance visual display.